My lastcouple mentions of viral immune evasion of T cells may have left the impression that immune evasion in general has a minor contribution to viral pathogenicity. Far from it. There are lots of examples — some very dramatic (I know of a couple really spectacular experiments that aren’t yet published) — of viral immune evasion genes that are important, or essential, for virulence. One example is influenza virus’s evasion of interferon.

Everyone’s heard of influenza. It’s a relatively small RNA virus with many different strains, which differ in their virulence, host range, antigenicity, and so forth. As with many viruses, the interferon response (part of the innate immune system) can be a very powerful inhibitor of virus infection, and so it’s not surprising that influenza has evolved a way around interferon. It does this by means of a non-structural protein, NS1, which prevents interferon induction in infected cells. How important is this protein to viral infectivity, in vivo?

The experiment has been done in a number of species. (One nice thing about influenza, from the researcher’s viewpoint, is that it does infect many different species, including some — mice, chickens, pigs — which are relatively easy to study.) For example, Donelan et al1 made a mutant influenza virus that lacks the NS1 protein, and looked at its virulence in mice. Wild-type influenza infection made the mice very sick: they lost weight (Figure to the right here; the diamond traces are the wild-type virus) and, around day 5, died of the infection, but mice infected with the mutant virus didn’t lose any weight (squares). As well, the virus replicated thousands of times worse in the mice. Although in this case mice aren’t the natural host of the virus, there are similar findings in, for example, chickens using avian influenza viruses2 so it’s pretty clear that this is an authentic virulence factor.

Speaking of avian influenza (nice segue, eh?), we all know about the concerns about an avian influenza pandemic. One of the reasons for the fear of this virus is previous experience with avian influenza in humans. In 1997, H5N1 influenza viruses jumped from chickens to humans and proved to be highly virulent — this was the Hong Kong outbreak of avian influenza, in which something like 6 of 18 known-infected people died. 3 It turns out that the NS1 in this H5N1 virus somehow is even more potent than normal, wild-type, virus in its ability to block the effects of interferon.4 Taking the H5N1 NS1 gene, and plugging it into a generic influenza virus (PR8, the most common lab strain) turned the normally fairly-innocuous PR8 virus into a vicious bastard, causing nearly a 50% weight loss in infected pigs (the circles in the figure to the left; the squares and triangles show the weights of pigs infected either with wild-type PR8, or with PR8 containing a mutated version of the H5N1 NS1). (The adorable pig pictures at the top of this post are from a later paper by the same authors.5 )

So immune evasion genes can be really potent virulence factors, which really contrasts to the apparently-minor effects of the CTL immune evasion genes.

[…] iayork wrote a fantastic post today on “Effective immune evasion (Influenza vs. Interferon: The grudge match)”Here’s ONLY a quick extractFor example, Donelan et al1 made a mutant influenza virus that lacks the NS1 protein, and looked at its virulence in mice. Wild-type influenza infection made the mice very sick: they lost weight (Figure to the right here; … […]

[…] of immune evasion that do have a very large effect on the virus’s virulence. The example I mentioned before was influenza virus. Different strains of influenza virus are more or less able to prevent innate […]

[…] of course, has its own set of immune evasion genes. The most important one is the NS1 gene.2 NS1 blocks the interferon pathway, and to the extent that we can generalize, it seems that blocking interferon is one of the most […]

[…] of course, has its own set of immune evasion genes. The most important one is the NS1 gene.2 NS1 blocks the interferon pathway, and to the extent that we can generalize, it seems that blocking interferon is one of the most […]

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